Aggressive Melanoma is on the rise in the U.S. It is imperative to discover new forms of therapy for melanoma. Effective therapy for melanoma can be performed by using cytotoxic agents, immunostimulating agents, chemotherapeutics, recombinant protein, and recombinant DNA. A major part of cancer treatment involves successful delivery of the desired agent. One such delivery method is in vivo electroporation, which uses electric fields in order to allow the cell membrane of melanoma cells to become permeabilized. Once the membrane is permeabilized, plasmid encoding Vpr is introduced into the melanoma cells by direct intratumoral injection on C57B1/6 mice. Vpr, the HIV-1 protein, has been implicated in several cellular functions: G2 arrest in T cells, apoptosis of T cells, and inhibition of melanoma growth in a mouse model. The hypothesis of this work is that the combination of Vpr plasmid and electroporation leads to regression of established BI6 melanoma in the mouse model. The specific aims of this research are three-fold: to elucidate a mechanism regarding the ability of Vpr to inhibit tumor growth in vivo; to demonstrate the optimal dosage of Vpr plasmid required for efficient tumor reduction; and to determine whether Vpr plasmid induces an immunological response, allowing the treated mice to be resistant to tumor challenge. Since in vivo electroporation offers a method of targeting melanoma tumors as well as a variety of tumor cell lines, further research can be conducted using this protocol to treat mice bearing squamous-cell carcinoma.